The Hiyama Reaction

SCHEME 19.46 Construction of the biaryl unit in vancomycin aglycon via a Suzuki-Miyaura reaction [64]. 

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Reactions with Organosilicon Reagents The Hiyama Reaction... 

The coupling of organosilicon compounds with organic electrophiles was not disclosed until 1988 by Hatanaka and Hiyama, when they demonstrated that through the addition of an appropriate silicophilic nucleophile, those desired pentacoordinate species can be generated in situ and transfer an unsaturated group. Nucleophilic fluoride sources were found to be the additive of choice, typically TASK, TBAF, and, in some cases, KF and GsF. These are the fundamental concepts of what is nowadays called the Hiyama reaction. The use of fluoride... 

Coupling of organosilane derivatives to RX species is known as the Hiyama reaction. This process is seen as more difficult to catalyze than the Stille reaction since a C-Si bond is less reactive than a C-Sn bond. However, addition of additives, such as B114NF or CsF, that form hypervalent silicon intermediates, or the use of more reactive silane precursors, such as Me3SiSiMc3, ArSiMc20H, or Cl2MeSi(vmyl), can overcome this limitation (equation 29). 

TBAF can promote hiaryl formation from triaflyl(aryl)silanes and a wide variety of aryl halide suhstrates. For example, chlorobenzenes undergo smooth cross-couphng with triallyl(aryl)silanes to give biaryls in good to excellent yields (eq 31). Surprisingly, an appreciable amount of added water is required to achieve high yields however, the role of added water is not yet clear.In a recent variant of the Hiyama reaction, TBAF and palladium-coated nickel nanoclusters were employed to prepare biaryl compounds from aryl bromides and phenyltrimethoxysilane. ... 

Summary This is an exampie of the Hiyama reaction which coupies an organosiiane and a organohaiide under paiiadium cataiysis ... 

Transmetallation of alkenylsilanes takes place with retention of the double bond configuration, as in other cross-coupling reactions [295]. Owing to the lower transmetallation rate, competing 1,2-insertion of the alkene in the intermediate organopalladium complex (as a Heck type reaction) may take place, which affects the regioselectivity of the Hiyama reaction in some cases (Scheme 1.38) [296]. This... 

Scheme 1.38 The Hiyama reaction involving alkene insertion (as a Heck type reaction) before transmetallation.

SCHEME 19.49 Mechanism of the Hiyama reaction performed in the presence of nBu NR... 

With the discovery of the Hiyama reaction other cross-coupling partners such as organosilicon derivatives have recently emerged as excellentreagents. 75 Various silicon substituted derivatives are suitable for transmetallation step when fluoride ions are added in the reaction medium. Organofluorosilanes bearing aryl, vinyl, or... 

To date, nearly all studies of the Hiyama reaction have focused on couplings of Csp -X electrophiles. Fu developed the first method for achieving the room-temperature Hiyama couplings of unactivated alkyl bromides and iodides. Palladium-catalyzed reactions of alkyl bromides and iodides 18 with aryltrimethoxysilanes 19 in the presence of phosphorus ligand and TBAF afforded coupled products 20 in moderate to good yields. 

Tadano utilized the Hiyama reaction in a formal synthesis of the antimicrobial tricyclic macrolides tubelactomicins. The intramolecular Hiyama cross-coupling reaction of 64 aided in the synthesis of a 24-membered macrolactone equipped with all the requisite functionalities, which then triggered the transannular Diels-Alder reaction to give 65. The 24-membered lactone formation was also achieved by the intramolecular ring-closing metathesis reaction. 

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